Annual Report 2015 (updated version)

Transcription

1 UniversitätsKlinikum Heidelberg Universitätsklinik für Kinder- und Jugendmedizin Stoffwechselzentrum Heidelberg Stoffwechsellabor Im Neuenheimer Feld Heidelberg To University Children s Hospital Angelika-Lautenschläger-Klinik Department of General Pediatrics (General Pediatrics, Neurology, Metabolism, Gastroenterology, Nephrology) Prof. Dr. med. G.F. Hoffmann Chairman Center for Metabolic Diseases Heidelberg Metabolic Laboratory Heidelberg, 21.April 2016 ERNDIM QA Scheme for qualitative urinary organic acid analysis Participation Annual Report 2015 (updated version) The geographical distribution of the active participants of the quality assurance scheme organized and distributed through the centre of Heidelberg in 2015 is shown in Table 1. Sheffield and Heidelberg participate in each other s scheme and the two centers work closely together under the auspices of the ERNDIM Scientific Advisory Committee. Table 1: Geographical distribution of participants Country Number of Number of Country laboratories laboratories Austria 3 Latvia 1 Belgium 1 Lithuania 1 Bulgaria 1 Luxembourg 1 Canada 8 New Zealand 1 Croatia 1 Norway 1 Cyprus 1 Philippines 1 Czech Republic 2 Poland 2 Denmark 1 Serbia 1 Estonia 1 Slovakia 2 France 5 Slovenia 1 Germany 17 Spain 2 Greece 1 Sweden 2 Hong Kong 1 Switzerland 3 Hungary 1 The Netherlands 9 India 4 Ukraine 1 Italy 12 United Kingdom 1 Kingdom of Saudi Arabia 2 USA 12 Im Neuenheimer Feld Heidelberg Stoffwechsellabor: Fon +49 (0) Fax +49 (0) Neugeborenenscreening: Fon +49 (0)

2 Page 2 of 13 Samples and results Three sets of three samples (total 9; sample numbers ) were distributed to 104 laboratories. One laboratory registered as educational participant and was not scored. Table 2 shows the number of returned results for each circulation and the number of late returns. Table 2: Receipt of results Circulation In time returns Late returns Total 1. circulation circulation circulation Ninety-four percent of the participants returned results for all three circulations. Three laboratories (3%) did not respond to any of the circulations (see also table 3) Table 3: returned results Circulations Number of laboratories % Shipment of the samples Date of sample dispatch: 04 May 2015 For the first time the nine urine samples were sent out by the Quality Control Center Switzerland (CSCQ). As the years before the samples for all three circulations were shipped together. This is only for organizational reasons, especially to keep the costs for participating in this scheme as low as possible. Please remember, the idea of the scheme is to measure the samples evenly spread over the year and to report the results near to the closing date!

3 Page 3 of 13 Table 4: Distribution of scores for individual samples (number of laboratories making returns) Sample 223 Canavan disease Sample 224 Isovaleric aciduria Sample 225 Normal pattern 97 1 Sample 226 Normal pattern 99 1 Sample 227 Maple syrup urine disease (MSUD) Sample 228 Mevalonic aciduria 100 Sample 229 Normal pattern 98 Sample 230 Alkaptonuria Sample oxoprolinuria 98 Scoring scheme In the process of ongoing accreditation of the ERNDIM organization there is a need for harmonization of performance assessment within the qualitative schemes (see ERNDIM Newsletter Spring 2013 at In 2013 we changed the scoring system from the former scale (-2, -1, 0, +1, +2) to the fourpoint system (+1, +2, + 3, +4) which is used also in the DPT schemes. In this system a maximum of two points is given each for analytical results and interpretation, with the latter including suggestions for further testing/actions. The total score achievable for a single circulation of three samples is twelve and thirty-six for the whole sample set of nine samples per year. To obtain satisfactory performance a score of 22 or more should be achieved on three returns and 15 or more when two returns have been submitted. Another criteria for satisfactory performance will be the absence of any critical error which is defined as an error resulting from seriously misleading analytical findings and /or interpretations with serious clinical consequences for the patient. Comments on performance Sample 223: 15-month old girl with muscle hypotonia and motor retardation Canavan disease

4 Page 4 of 13 Analytical details In the chromatogram elevated amounts of 3-hydroxybutyric acid and lactic acid as well as a marked dicarboxyluria could be found. To make the correct diagnosis the detection of increased amounts of N-acetylaspartic acid was essential. This metabolite forms on trimethylsilylation two derivatives, namely the di-tms and the tri-tms derivative.

5 Page 5 of 13

6 Page 6 of 13 Analytical Performance: 90%. Two points was given for the identification of N- acetylaspartic acid and one point for only 3-hydroxybutyric acid and lactic acid. Diagnostic Performance: 87%. One point was given for the diagnosis of ketosis, lactic acidosis or mitochondrial disease. Overall impression: Ten percent of the laboratories have difficulties in extracting N- acetylaspartic acid Critical error: A critical error was defined if detection of N-acetylaspartic acid was missed or a misleading diagnosis was given with no advice for further investigations. Sample 224: 3-year old boy presenting with recurrent vomiting, first detected in newbornscreening, at present under medication Isovaleric aciduria / isovaleryl-coa dehydrogenase deficiency A large peak of isovalerylglycine clearly pointed to isovaleric aciduria. Normal 3-hydroxyisovaleric acid indicates a non-crisis situation. Overall Performance: 100%. All participants clearly detected isovalerylglycine and diagnosed isovaleric aciduria. Sample 225: 3-year old boy with developmental delay Normal pattern Nothing specific Overall Performance: 99% Sample 226: 2-year old girl presented with hypotonia and seizures Normal pattern Nothing specific Overall Performance: 99%

7 Page 7 of 13 Sample 227: 4-year old girl with developmental delay, first detected in newbornscreening, currently under medication Maple syrup urine disease (MSUD) The chromatogram showed pathologically elevated amounts of several branched chain oxo- and hydroxy acids, especially 2-hydroxyisovaleric acid, 2-hydroxy- 3-methylvaleric acid, 2-oxoisovaleric acid, 2-oxo-3-methylvaleric acid and 2-oxoisocaproic acid. Overall Performance: 98%. Two laboratories had problems in identifying the branched chain oxo- and hydroxy acids Critical error: A critical error was defined if detection of branched chain oxo- and hydroxyacids was missed or a misleading diagnosis was given with no advice for further investigations. Sample 228: 1-year old boy with hypotonia and dysmorphia Mevalonic aciduria

8 Page 8 of 13 The pathognomonic metabolite mevalonic acid manifested in the chromatogram in different derivatives. Beside underivatised dehydromevalonolactone and mevalonolactone one could found the tri-trimethylsilyl derivative of mevalonic acid and the mono-trimethylsilyl derivative of mevalonolactone. The latter is the main product formed under the used sample preparation conditions. Overall Performance: 100%. All participants identified the relevant metabolite and gave the correct diagnosis Sample 229: 1-year old boy with failure to thrive Normal pattern Nothing specific Overall Performance: 100% Sample 230: Analytical Performance: 16-year old female complain of nausea and drowsiness Alkaptonuria The chromatogram showed a large peak of homogentisic acid 99%. One laboratory failed to detect homogentisic acid Diagnostic Performance: 98%

9 Page 9 of 13

10 Page 10 of 13 Sample 231: Overall Performance: neonate with psychomotor retardation 5-oxoprolinuria The chromatogram showed a large peak of 5-oxoproline 100%. All participants identified the relevant metabolite and gave the correct diagnosis The participants cumulative scores are shown in table 6 and in figure 5. Cumulative scores are the scores for the whole year. In 2015 eighty participants (81%) got full marks!

11 Page 11 of 13 Table 6: Cumulative total scores Number of all participants: all registered laboratories Number of nonresponders: no results returned for any of the three circulations Percent of all participants Cumulative scores Number of all participants Number of Nonresponders 3 2 3

12 Page 12 of 13 Fig. 6: Cumulative scores 2015 Your total score 2015 Your total score for 2015 was: Your number of returns in 2015 was:

13 Page 13 of 13 General comments We would just like to point out here that we are not able to accept returns sent in after the report for the corresponding circulation has been mailed because this would not be compatible with the overall intention of the scheme. We are conscious of the fact that posted results could get lost on a variety of ways. Therefore it would be a good advice to send in results by more than one route (e.g. FAX and , regular mail and FAX or ). Special thank for the laboratories that supported us last year with samples. This is critical for the success of the program and will keep the scheme interesting. It is most appreciated that you will continue to support us with urine from patients. Please send us at least 300 ml urine of any interesting patients you may have. We will cover the costs. Yours sincerely, Dr. C. D. Langhans Dr. V. Peters Prof. Dr. G. F. Hoffmann Director Laboratory of Metabolic Laboratory of Metabolic Department of General Diseases Diseases Paediatrics